Prostate-specific membrane antigen expression in the duodenum: implications in coeliac disease and immunotherapy for prostate cancer

Maraj, BH; Aldersley, M.; Markham, AF

doi:10.1016/s0140-6736(05)61125-7

Cited by 13 publications

(8 citation statements)

References 2 publications

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“…In the preclinical literature, PSMA expression has been described for the proximal small intestine (27,30). However, in agreement with our experiences with PSMA-11, all of our patients additionally showed PSMA-617 uptake in parts of the colon as well.…”

Section: Discussionsupporting

confidence: 91%

The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions

et al. 2015

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Section: Discussionsupporting

confidence: 91%

The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions

et al. 2015

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“…Prostate tissue and prostate cancer express several potential target Ags, including prostate-specific Ag (PSA), 4 prostate-specific membrane Ag, and prostatic acid phosphatase (PAP). Although PSA and prostate-specific membrane Ag have been detected in other tissues (7)(8)(9), PAP appears to be restricted in its tissue distribution to the prostate and prostate carcinoma (10). mAbs with specificity for PAP stain only normal prostate and prostate cancer cells (11), and the use of PAP cDNA to probe Northern blots from a variety of tissues revealed PAP RNA only in benign and malignant prostate cells (12).…”

mentioning

confidence: 99%

Dendritic Cell-Based Xenoantigen Vaccination for Prostate Cancer Immunotherapy

Fong

Brockstedt

Benike

et al. 2001

The Journal of Immunology

229

132

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Many tumor-associated Ags represent tissue differentiation Ags that are poorly immunogenic. Their weak immunogenicity may be due to immune tolerance to self-Ags. Prostatic acid phosphatase (PAP) is just such an Ag that is expressed by both normal and malignant prostate tissue. We have previously demonstrated that PAP can be immunogenic in a rodent model. However, generation of prostate-specific autoimmunity was seen only when a xenogeneic homolog of PAP was used as the immunogen. To explore the potential role of xenoantigen immunization in cancer patients, we performed a phase I clinical trial using dendritic cells pulsed with recombinant mouse PAP as a tumor vaccine. Twenty-one patients with metastatic prostate cancer received two monthly vaccinations of xenoantigen-loaded dendritic cells with minimal treatment-associated side effects. All patients developed T cell immunity to mouse PAP following immunization. Eleven of the 21 patients also developed T cell proliferative responses to the homologous self-Ag. These responses were associated with Ag-specific IFN-gamma and/or TNF-alpha secretion, but not IL-4, consistent with induction of Th1 immunity. Finally, 6 of 21 patients had clinical stabilization of their previously progressing prostate cancer. All six of these patients developed T cell immunity to human PAP following vaccination. These results demonstrate that xenoantigen immunization can break tolerance to a self-Ag in humans, resulting in a clinically significant antitumor effect.

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“…We sought to reduce toxicity through encapsulation of an antiandrogen in a PSMA-conjugated nanoparticle. PSMA, prostate-specific membrane antigen, is only expressed on prostate epithelium, duodenal mucosa, and a subset of the proximal renal tubules 41 and thus has been an attractive biomarker for prostate cancer specificity. PSMA is nearly universally expressed in the hormone sensitive setting of the disease, and PSMA expression is increased in the setting of androgen deprivation therapy.…”

Section: Discussionmentioning

confidence: 99%

Improvement in Therapeutic Efficacy and Reduction in Cellular Toxicity: Introduction of a Novel Anti-PSMA-Conjugated Hybrid Antiandrogen Nanoparticle

et al. 2018

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Second generation antiandrogens have improved overall survival for men with metastatic castrate resistant prostate cancer; however, the antiandrogens result in suppression of androgen receptor (AR) activity in all tissues resulting in dose limiting toxicity. We sought to overcome this limitation through encapsulation in a prostate specific membrane antigen (PSMA)-conjugated nanoparticle. We designed and characterized a novel nanoparticle containing an antiandrogen, enzalutamide. Selectivity and enhanced efficacy was achieved through coating the particle with PSMA. The PSMA-conjugated nanoparticle was internalized selectively in AR expressing prostate cancer cells. It did not elicit an inflammatory effect. The efficacy of enzalutamide was not compromised through insertion into the nanoparticle; in fact, lower systemic drug concentrations of enzalutamide resulted in comparable clinical activity. Normal muscle cells were not impacted by the PSMA-conjugated containing antiandrogen. This approach represents a novel strategy to increase the specificity and effectiveness of antiandrogen treatment for men with castrate resistant prostate cancer. The ability to deliver higher drug concentrations in prostate cancer cells may translate into improved clinical end points including overall survival.

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Prostate-specific membrane antigen expression in the duodenum: implications in coeliac disease and immunotherapy for prostate cancer

Cited by 13 publications

References 2 publications

The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions

The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions

Dendritic Cell-Based Xenoantigen Vaccination for Prostate Cancer Immunotherapy

Improvement in Therapeutic Efficacy and Reduction in Cellular Toxicity: Introduction of a Novel Anti-PSMA-Conjugated Hybrid Antiandrogen Nanoparticle

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